Clinicalstudiesinhumanshaverevealedadeleteriouseffectofaldosteroneoncardiovascularfunctionindependentofitseffectsonrenalsodiumandwaterreabsorption.Aldosteronehasaproinflammatory, profibrotic effect onthecardiovascularsystemandcausesleftventricularhypertrophyandremodeling.Thiseffectofaldosteroneisassociatedwithincreasedmorbidityandmortalityinpatientswithessentialhypertension.
Physiological Actions of Aldosterone
The actions and regulation of aldosterone are discussed in
CHAPTER 43 The Adrenal Gland •Fig. 43.15 Steroidogenicpathwaysinthezonaglomerulosa.Thefirstcommonreactioninthepathway,conversionofcholesteroltopregnenolonebyCYP11A1,isnotshown.NotethatthelastthreereactionsarecatalyzedbyCYP11B2.(ModifiedfromWhiteBA,PorterfieldSP.EndocrineandReproductivePhysiol-ogy.4thed.Philadelphia:Mosby;2013.)CH3 CH3 CH3 Pregnenolone C O 3˜-HSD CH3 CH3 CH3 Progesterone C O CYP21B HO CH3 CH3 CH2OH 11-Deoxycorticosterone (DOC) C O CYP11B2 CH3 CH3 CH2OH Corticosterone C O CYP11B2 O HO HO CH3 CH3 CH2OH 18(OH) Corticosterone C O CYP11B2 O HO CH3 CH2OH Aldosterone C O O O CH
Addison’s disease isdefinedbyprimary adrenal insufficiency, withbothmineralocorticoidsandglucocorticoidsusuallybeingdeficient.InNorthAmericaandEurope,themostprevalentcauseofAddison’sdiseaseisautoimmune destruction of the adrenal cortex. Becauseofthecortisoldeficiency,ACTHsecretionincreases.ElevatedlevelsofACTHcancompeteforMC1Rinmelanocytesandcauseanincreaseinskinpigmentation,particularlyinskincreases,scars,andgums(see
Fig.43.14 ).Thelossofmineralocorticoidsresultsincontractionofextracellularvolume,whichproducescirculatoryhypovolemiaandthereforeadropinbloodpressure.Becauselossofcortisoldecreasesthevasopressiveresponsetocatecholamines,peripheralvascularresistancedrops,therebyfacilitatingthedevelopmentofhypotension.IndividualswithAddison’sdiseasearealsopronetohypoglycemiawhenstressedorfasting,andwaterintoxicationcandevelopifexcesswaterisingested.Becausecortisolisimportantformusclefunction,muscleweaknessalsooccursincortisoldeficiency.Lossofcortisolresultsinanemia,decreasedGImotilityandsecretion,andreducedironandvitaminB12absorption.Appetitedecreaseswithcortisoldeficiency,andthisdecreasedappetitecoupledwiththeGIdysfunctionpredisposestheseindividualstoweightloss.Thesepatientsoftenhavedisturbancesinmoodandbehaviorandaremoresusceptibletodepression.